THE 2.9 LIPOPROTEIN FAMILY OF BORRELIA BURGDORFERI

描述（改编自申请人的摘要）：莱姆病，由以下引起： 致病性伯氏疏螺旋体（Borreliaburgdorferi，Bb）是一种主要公共卫生 需要进一步努力发展的问题 疫苗和新的诊断方法。调查人员发现了一个新的家庭， 脂蛋白（称为“2.9”脂蛋白），似乎是“差异 表示为”由Bb表示“;即，这些脂蛋白中的一些表示为Bb 体外重复（类似于Bb生命周期的节肢动物阶段） 而其它的表达为“体内”Bb复制（即，期间 感染的哺乳动物阶段）。令人信服的初步数据已经支持 期望那些“体内”表达的2.9种脂蛋白可以作为 有效的疫苗和血清诊断试剂。 本建议的具体目的是：（1）确定和比较“在 Bb的2.9脂蛋白的“体外”与“体内”表达模式 （2）评估2.9种脂蛋白（特别是那些 在“体内”条件下由Bb表达）在Bb中表面暴露， 保护性抗体的靶（即，候选疫苗）;（3） 探讨2.9脂蛋白作为莱姆病血清学诊断新抗原的可行性 疾病;和（4）检查同源2.9脂蛋白的存在 （特别是具有疫苗和诊断重要性的那些） 广义基因种为B。伯格多费里。 这个提议的一个特别新颖的方面是它依赖于一种新的动物 模型系统，其中可以获得毒性的“哺乳动物宿主适应的”Bb 从大鼠或兔腹膜腔中取出，其量足以鉴定2.9 Bb的脂蛋白在体内表达。“利用这些新动物 用于区分“体外”与“体内”表达的模型系统 2.9脂蛋白的模式在于， 可以选择性地选择Bb的人畜共患病生活史的每个或两个阶段， 解决莱姆病疫苗开发中的当代问题， 血清学诊断

DESCRIPTION (Adapted from the Applicant's Abstract): Lyme disease, caused by the pathogenic spirochete Borrelia burgdorferi (Bb) is a major public health problem which warrants further efforts towards the development of improved vaccines and new diagnostics. The investigators have discovered a new family of lipoproteins (termed "2.9" lipoproteins) that appear to be "differentially expressed" by Bb; i.e., some of these lipoproteins are expressed as Bb replicates in vitro (analogous to the arthropod phase of Bb's life cycle) whereas others are expressed as Bb replicates "in vivo" (i.e., during the mammalian phase of infection). Compelling preliminary data already support the expectation that those 2.9 lipoproteins expressed "in vivo" may serve as effective vaccines and serodiagnostic reagents. The Specific Aims of this proposal are: (1) To determine and compare the "in vitro" versus "in vivo" expression patterns for the 2.9 lipoproteins of Bb strain 297; (2) To assess whether the 2.9 lipoproteins (particularly those express by Bb under "in vivo" conditions) are surface-exposed in Bb and thus targets for protective antibodies (i.e., vaccine candidates); (3) To investigate the 2.9 lipoproteins as new antigens for the serodiagnosis of Lyme disease; and (4) To examine the presence of homologous 2.9 lipoproteins (particularly those with vaccinogenic and diagnostic importance ) in all three sensu lato genospecies of B. burgdorferi. A particularly novel aspect of this proposal is its reliance upon a new animal model system in which virulent, "mammalian host-adapted" Bb can be obtained from rat or rabbit peritoneal chambers in quantities sufficient to identify 2.9 lipoproteins of Bb expressed "in vivo." The power of utilizing these new animal model systems for sorting out the "in vitro" versus "in vivo" expression patterns for 2.9 lipoproteins lies in the fact that antigens expressed during each or both phases of the zoonotic life cycle of Bb can be selectively chosen to address contemporary issues in Lyme disease vaccine development and serodiagnosis.